Cortical Excitability Can Differentiate Migraine Types

Abstract & Commentary

By Dara Jamieson, MD, Associate Professor of Clinical Neurology, Weill Cornell Medical College. Dr. Jamieson reports she is a retained consultant for Boehringer Ingelheim, Merck, and Ortho-McNeil, and is on the speakers bureau for Boehringer Ingelheim.

Synopsis: Migraine patients show impairment in the processing of global visual features, compared with controls, both between and immediately after an attack. The pattern of ictal-interictal potential as noted on magnetoencephalography studies can characterize different migraine types.

Sources: Koppen H, et al. The impact of a migraine attack and its after-effects on perceptual organization, attention, and working memory. Cephalalgia 2011 Aug 4 [Epub ahead of print]. Chen WT, et al. Sustained visual cortex hyperexcitability in migraine with persistent visual aura. Brain 2011;134:2387-2395.

Many migraine patients report cognitive complaints during the hours or days following a migraine attack. The aim of this study from the Netherlands was to assess the degree to which a recent migraine attack affects cognitive functions at different processing levels. Migraineurs with and without aura (n = 16) were given experimental tasks at three points in time post-ictally and their performance was compared with 18 healthy matched controls. Cognitive (perceptual, attentional, or memory) processes were assessed during the first headache-free day following a migraine attack, 24 hours later, and 12 days after the attack. The tasks measuring sustained and selective attention showed no significant differences between migraineurs and controls. In the global-local task (assessing perceptual organization capabilities), controls showed faster reaction times to global than to local stimuli, which is the standard global-precedence effect. This effect was absent in the migraineurs in all three sessions, especially if they used prophylactic medication for headache suppression. Migraineurs had no impaired attentional or working-memory functioning in the two days after an attack. They did show impairments in the processing of global visual features compared with controls, both between and immediately after an attack.

Persistent aura without infarction, a rare migraine disorder, is defined by aura symptoms that persist for more than a week, without radiological evidence of cerebral infarction. The visual cortex in persistent visual aura may be dominated by the sustained, recurrent excitatory activations mediating cortical spreading depression waves, which dampen the habituation phenomenon in the cerebral cortex. This study by Chen et al used magnetoencephalography to characterize the visual cortex excitability in patients with persistent aura, as compared to those with episodic and chronic migraine. Six patients with persistent visual aura, 39 patients with episodic migraine (12 in ictal phase; 27 in interictal phase [with aura, n = 9; without aura, n = 18]), 18 patients with chronic migraine, and 24 healthy controls underwent recording of visual-evoked magnetic fields using pattern reversal white and black checkerboard stimuli. Five sequential blocks of 50 neuromagnetic prominent 100 ms responses were obtained. The dynamic change in visual cortex excitability was evaluated by the percentage changes of individual mean prominent 100 ms amplitudes at blocks 2-5 compared with block 1, with a significant increase indicating potentiation. In patients with persistent aura, there was significant potentiation during ictal periods and the excitability change was inversely correlated with the duration of aura persistence. The interictal recordings in patients with persistent aura also showed potentiation. Persistent aura differed from episodic migraine in the presence of ictal potentiation. Persistent aura further differed from chronic migraine in the absence of interictal potentiation in chronic migraine. There was a higher percentage change of response amplitude at the end of stimulation in persistent aura than in chronic migraine and ictal recordings of episodic migraine. Normal control subjects had no significant response changes. The authors concluded that the study showed that persistent visual aura is characterized by persistent hyperexcitability of the visual cortex without interictal-ictal variation, compatible with the excitatory effect of sustained reverberations of cortical spreading depression.

Commentary

These two papers illustrate that the effect of a migraine goes well beyond the pain of a headache, with manifestations of migraine that are related to alterations in cortical processing and central excitability. Although migraine patients often complain about cognitive impairment shortly after a migraine attack, no temporal negative effect on cognitive function after the attack was found in this study. However, differences between migraine patients and controls were observed with respect to the organization of local and global visual stimuli. This task difficulty was not a function of time after a migraine attack, suggesting that the difference from controls was not related to the migraine attack per se, but was related to the predisposition toward migraines or to the use of preventive medications.

Chen et al posit that migraines with and without aura, in the interictal state, are characterized by the lack of habituation and that the cortical responses to repetitive sensory stimulations may be potentiated. They studied "persistent aura without infarction," which is recognized in the International Headache Society classification but is exceedingly rare, making the study of six patients exceptional. The visual cortex hyperexcitability of patients with persistent visual aura showed significant potentiation in response to repetitive visual stimulations across ictal-interictal periods. The potentiation pattern in persistent visual aura was also found in interictal migraine with and without aura; however, it was not observed during the ictal migraine state, suggesting the excitability change in migraine with and without aura differs from that of persistent visual aura in terms of ictal-interictal modulations. The vicious cycle of sustained cortical spreading depression formed in persistent visual aura may lead to excessive neuronal stress with accumulation of metabolites that induce repetitive cortical spreading depression. This distinct ictal-interictal potentiation pattern suggests that persistent visual aura is on the migraine spectrum but may differ from other migraine disorders (migraine with aura, migraine without aura, and chronic migraine). The complex interaction between cortical spreading depression and central excitability is common across the migraine spectrum; but, aspects of extent and timing may help to define specific migraine types. These two studies serve to illustrate the complexity of this fascinating, neuronally mediated disease.